Zaleplon

Zaleplon capsules are indicated for the short-term treatment of insomnia. Zaleplon capsules have been shown to decrease the time to sleep onset for up to 30 days in controlled clinical studies. They have not been shown to increase total sleep time or decrease the number of awakenings. The clinical trials performed in support of efficacy ranged from a single night to 5 weeks in duration. The final formal assessments of sleep latency were performed at the end of treatment.

While zaleplon is a hypnotic agent with a chemical structure unrelated to benzodiazepines, barbiturates, or other drugs with known hypnotic properties, it interacts with the gamma-aminobutyric acid-benzodiazepine (GABA-BZ) receptor complex. Subunit modulation of the GABA-BZ receptor chloride channel macromolecular complex is hypothesized to be responsible for some of the pharmacological properties of benzodiazepines, which include sedative, anxiolytic, muscle relaxant, and anticonvulsive effects in animal models. Other nonclinical studies have also shown that zaleplon binds selectively to the brain omega-1 receptor situated on the alpha subunit of the GABA A /chloride ion channel receptor complex and potentiates t-butyl-bicyclophosphorothionate (TBPS) binding.

The dose of zaleplon should be individualized. The recommended dose of zaleplon for most nonelderly adults is 10 mg. For certain low weight individuals, 5 mg may be a sufficient dose. Although the risk of certain adverse events associated with the use of zaleplon appears to be dose dependent, the 20 mg dose has been shown to be adequately tolerated and may be considered for the occasional patient who does not benefit from a trial of a lower dose. Doses above 20 mg have not been adequately evaluated and are not recommended. Zaleplon should be taken immediately before bedtime or after the patient has gone to bed and has experienced difficulty falling asleep. Taking zaleplon with or immediately after a heavy, high-fat meal results in slower absorption and would be expected to reduce the effect of zaleplon on sleep latency.

Zaleplon capsules are contraindicated in patients: who have experienced complex sleep behaviors after taking zaleplon capsules. with hypersensitivity to zaleplon or any excipients in the formulation.

Boxed warning (complex sleep behaviors): Complex sleep behaviors including sleep-walking, sleep-driving, and engaging in other activities while not fully awake may occur following use of zaleplon. Some of these events may result in serious injuries, including death. Discontinue zaleplon immediately if a patient experiences a complex sleep behavior. Zaleplon is a federally controlled substance (C-IV) because it can be abused or lead to dependence. Complex Sleep Behaviors Complex sleep behaviors including sleep-walking, sleep-driving, and engaging in other activities while not fully awake may occur following the first or any subsequent use of zaleplon. Patients can be seriously injured or injure others during complex sleep behaviors. Such injuries may result in a fatal outcome.

The premarketing development program for zaleplon included zaleplon exposures in patients and/or normal subjects from 2 different groups of studies: approximately 900 normal subjects in clinical pharmacology/pharmacokinetic studies, and approximately 2,900 exposures from patients in placebo-controlled clinical effectiveness studies, corresponding to approximately 450 patient exposure years. The conditions and duration of treatment with zaleplon varied greatly and included (in overlapping categories) open-label and double-blind phases of studies, inpatients and outpatients, and short-term or longer-term exposure. Adverse reactions were assessed by collecting adverse events, results of physical examinations, vital signs, weights, laboratory analyses, and ECGs.

As with all drugs, the potential exists for interaction with other drugs by a variety of mechanisms. CNS-Active Drugs Ethanol Zaleplon 10 mg potentiated the CNS-impairing effects of ethanol 0.75 g/kg on balance testing and reaction time for 1 hour after ethanol administration and on the digit symbol substitution test (DSST), symbol copying test, and the variability component of the divided attention test for 2.5 hours after ethanol administration. The potentiation resulted from a CNS pharmacodynamic interaction, zaleplon did not affect the pharmacokinetics of ethanol. Imipramine Coadministration of single doses of zaleplon 20 mg and imipramine 75 mg produced additive effects on decreased alertness and impaired psychomotor performance for 2 to 4 hours after administration. The interaction was pharmacodynamic with no alteration of the pharmacokinetics of either drug.

Store at 20° to 25°C (68° to 77°F), excursions permitted to 15° to 30°C (59° to 86°F).